1,720,973 research outputs found
Genese des Mammakarzinoms in einem induzierbaren WAP-T-transgenen Mausmodell
No full textBrustkrebs gehört zu den häufigsten malignen Erkrankungen der westlichen Welt. Trotz zahlreicher bekannter Faktoren ist die Genese des Mammakarzinoms bislang weitestgehend
ungeklärt. Insbesondere die Klassifikation und Therapie von Präneoplasien, die als Folge verbesserter diagnostischer Möglichkeiten immer häufiger identifiziert werden, ist somit in vielen Fällen erschwert. Es besteht daher ein dringender Bedarf an adäquaten Tiermodellen, um frühe Stadien der Brustkrebsentstehung und deren Progression untersuchen zu können. In der vorliegenden Arbeit wurde die SV40-abhängige Entwicklung muriner Mammakarzinome in einem WAP-T-transgenen Mausmodell anhand histopathologischer und
molekularbiologischer Methoden untersucht. Es handelt sich dabei um ein induzierbares Mausmodell, bei welchem die frühe Region des SV40 unter der Kontrolle des
WAP-Promoters steht. Wie die hier vorgelegten Daten zeigen, fand eine gewebespezifischen Transgenexpression in Epithelzellen der Brustdrüsen erst unter dem Einfluß
laktotroper Hormone statt. Als Folge der Transgenexpression entwickelten sich präneoplastische Läsionen der Brustdrüsen. In einer Zeitreihe konnte die schrittweise Entdifferenzierung der Brustdrüsenepithelien im Rahmen der Karzinogenese von initialen morphologischen Veränderungen unter dem Einfluß des Transgens bis zur Entstehung invasiver Karzinome belegt werden. Die drei untersuchten Mauslinien erkrankten verglichen mit der Kontrollgruppe signifikant häufiger an Adenokarzinomen der Brustdrüse
und wiesen dabei eine linienspezifische Transgenexpression, Mammakarzinominzidenz und Latenzzeit bis zum Auftreten der Tumore auf. Da sich nicht alle Präneoplasien trotz konstanter Transgenexpression nach Induktion zu invasiven Karzinomen entwickelten, sondern auf Ebene von in situ Karzinomen vorerst zu einem Stillstand zu kommen schienen, konnte nachgewiesen werden, daß die Expression der frühen
Region des SV40 alleine zur malignen Transformation nicht ausreicht. Vielmehr fanden sich zahlreiche histopathologische und immunhistochemische Hinweise darauf, daß SV40 in WAP-T-transgenen Mäusen zu einer Immortalisierung epithelialer Progenitorzellen der Brustdrüse führte. Anhand LT-vermittelter Proliferation entwickelten sich anschließend intraepitheliale Neoplasien klonalen Ursprungs und erst nach Akkumulation weiterer onkogener Alterationen kam es zur Entstehung invasiver Mammakarzinome. Bei den entstehenden Tumoren handelte es sich um hormonrezeptornegative, überwiegend schlecht differenzierte Mammakarzinome, bei welchen ein luminal und ein basal differenzierter Phänotyp unterschieden werden konnte. Überdies ließ sich eine Beteiligung EMT-assoziierter Faktoren an der Entstehung der basalen Mammakarzinome vermuten. Das in dieser Arbeit beschriebene Mausmodell stellt somit nicht nur ein adäquates Modell
für eine nachvollziehbare, schrittweise Karzinogenese des Mammakarzinoms dar, sondern gibt zudem erste Hinweise auf die Beteiligung von Stamm- bzw. Progenitorzellen bei der Entstehung maligner Brustdrüsentumore
Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events
No full textIn KIT/PDGFRA wild-type gastrointestinal stromal tumors (wt-GISTs), BRAF mutations are regarded as alternative pathogenic events driving tumorigenesis. In our study, we aimed at analyzing a large cohort (n = 444) of GISTs for BRAF mutations using molecular and immunohistochemical methods. More than 3000 GIST samples from caucasian patients were available in our GIST and Sarcoma Registry NRW. Of these, we selected 172 wt-GISTs to evaluate the frequency of BRAF mutations. Furthermore, 272 GISTs with a representative KIT and PDGFRA mutational status were selected. BRAF mutational status was evaluated by high-resolution melting analysis, Sanger sequencing, and VE1 immunohistochemistry. A BRAF mutation (p.V600E) was found in 7 cases (3.9%) of the wt-GIST cohort. In 2 cases, multiple synchronous tumors harbored the same somatic BRAF mutation. VE1 immunohistochemical staining had a sensitivity of 81.8% and a specificity of 97.5% to detect BRAF p.V600E mutations. Analyzing our cases and the cases reported in the literature (n = 37), the percentage of intermediate and high-risk BRAF-mutated wt-GISTs (17/31; 54.8%) was comparable to that recorded for large GIST cohorts irrespective of the mutational status. BRAF mutations are rare events in wt-GISTs, and VE1 immunohistochemistry appears to be a valuable pre-screening tool for the detection of BRAF p.V600E mutations. BRAF mutations in GISTs do not seem to have a prognostic value per se. However, as BRAF inhibition represents a therapeutic option to control disease, we suggest the assessment of the BRAF mutational status, especially in the setting of advanced GIST disease. (C) 2017 Elsevier Inc. All rights reserved
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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